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PubMed2004

Squamous cell carcinoma of the bladder: pathology, diagnosis and treatment.

Squamous cell carcinoma (SCC) can occur in both nonbilharzial and bilharzial bladders; the two subtypes differ in epidemiology, pathogenesis and clinicopathological features. The nonbilharzial type occurs in Western countries and represents < 5% of all vesical tumours; it occurs most often in the seventh decade with a slight male predominance. The principal predisposing factor is prolonged indwelling urethral catheterization in patients with spinal cord injury and the main symptom is haematuria. Patients are usually diagnosed at an advanced stage and most of the tumours are of moderate and high grades. At cystoscopy tumours are predominantly ulcerative and commonly involve the trigone and lateral walls. Although distant metastasis is infrequent (8-10%) the prognosis is grave and most patients die after failure of locoregional control; radical cystectomy provides the best therapy. To avoid nonbilharzial SCC, patients with spinal cord injury should be free of catheterization if possible. The outcome can be improved by early detection with frequent cytology, cystoscopy and biopsy. Bilharzial SCC occurs commonly in the Middle East, South-east Asia and South America where schistosomiasis is endemic. In an Egyptian series SCC represented 59% of 1026 cystectomy specimens. The tumour is diagnosed in the fifth decade, and five times more common in men than women. Bladder carcinogenesis is probably related to bacterial and viral infections, commonly associated with bilharzial infestation rather than the parasite itself. The presentation is often with irritative bladder symptoms and haematuria, and many patients present at an advanced stage, although most tumours are of low and moderate grades. At cystoscopy tumours are predominantly nodular and usually arise from the upper vesical hemisphere. Lymph-node metastasis occurs in approximately 19% and significantly decreases survival; radical cystectomy remains the main treatment, giving a 5-year survival rate of 50%. Early detection improves the therapeutic yield and prevention is possible by combining snail control and mass therapy of the infested rural population by oral antibilharzial drugs.

Carcinoma, Squamous Cell↗

PubMed2006

Polymerase chain reaction-based identification of Propionibacterium acnes types isolated from the male urinary tract: evaluation of adolescents, normal adults and men with prostatic pathology.

OBJECTIVE: To assess whether colonization of the male urinary tract with Propionibacterium acnes, in particular types IB and II (which are associated with inflammation in radical prostatectomy specimens and might be involved in the development of prostate cancer), is associated with prostate disease, and thus to develop a urine test to detect men at risk of prostate disease. PATIENTS, SUBJECTS AND METHODS: We developed the first polymerase chain reaction (PCR)-based technique for identifying P. acnes types IA, IB and II, and used this in combination with selective culture medium to compare the prevalence of these subtypes in the urinary tract of adolescent males, healthy adult men and patients with confirmed prostate pathology. RESULTS: P. acnes types IB and II were no more prevalent in the urinary tract of patients with prostate pathology than in normal control men. However, the prevalence of types IB and II appeared to be higher in adult men (at 11 of 15 and six of 15, respectively) than in adolescents (two of six and one of six), suggesting an age-related increase. Comparison of urinary tract and facial skin P. acnes from three subjects showed that type IA was more often predominant on facial skin, whereas types IB or II were more often predominant in the urinary tract. CONCLUSIONS: A urine test might not be useful for detecting men with prostatic P. acnes infection and thus at greater risk of associated prostate disease. However, this work validated our technique for detecting and identifying the three P. acnes subtypes, and identified some interesting trends worth further investigation.

Adolescent↗

PubMed1992

Mediastinal large-cell lymphoma.

The records of 20 patients with pathologically diagnosed mediastinal large-cell lymphoma with sclerosis, a recently documented but uncommon subtype of mediastinal non-Hodgkin's lymphoma, were retrospectively reviewed to determine the clinical and radiologic features of the condition at the time of presentation. The disease was staged according to the Ann Arbor classification: 15 patients presented in clinical stage I or II and 5 in clinical stage III or IV. The patients, 6 women and 14 men, ranged in age from 15 to 63 years (mean = 31 years). Chest pain (experienced by 10 patients), dyspnea (by 9) and cough (by 7) were the most common clinical features. Obstruction of the superior vena cava occurred in seven patients. The mediastinal masses were large (the mean diameter was 10.8 cm) and located anteriorly (prevascularly). They contained low-attenuation areas and were often associated with other sites of mediastinal adenopathy. The initial pathologic diagnosis was incorrect for eight patients (40%). Mediastinal large-cell lymphoma can be added to the differential diagnosis of a large anterior mediastinal mass with obstruction of the superior vena cava.

Adolescent↗

PubMed2003

Epileptogenicity of focal malformations due to abnormal cortical development: direct electrocorticographic-histopathologic correlations.

PURPOSE: Malformations due to abnormal cortical development (MCDs) are common pathologic substrates of medically intractable epilepsy. The in situ epileptogenicity of these lesions as well as its relation to histopathologic changes remains unknown. The purpose of this study was to correlate the cellular patterns of MCDs with the expression of focal cortical epileptogenicity as assessed by direct extraoperative electrocorticographic (ECoG) recordings by using subdural grids. METHODS: Fifteen patients with drug-resistant focal epilepsy due to pathologically confirmed MCD who underwent subdural electrode placement for extraoperative seizure localization and cortical mapping between 1997 and 2000 were included in the study. Areas of interictal spiking and ictal-onset patterns were identified and separated during surgery for further pathologic characterization (cellular and architectural). Three pathologic groups were identified: type I; architectural disorganization with/without giant neurons, type IIA; architectural disorganization with dysmorphic neurons, and type IIB; architectural disorganization, dysmorphic neurons, and balloon cells (BCs). The focal histopathologic subtypes of MCDs in cortical tissue resected were then retrospectively correlated with in situ extraoperative ECoG patterns. RESULTS: Cortical areas with histopathologic subtype IIA showed significantly higher numbers of slow repetitive spike pattern in comparison with histopathologic type I (p = 0.007) and normal pathology (p = 0.002). The ictal onset came mainly from cortical areas with histopathologic type IIA (nine of 15 patients). None of the seizures originated from neocortical areas that showed BC-containing MCD (type IIB). CONCLUSIONS: This study shows that areas containing BCs are less epileptogenic than are closely located dysplastic regions. These results suggest a possible protective effect of BCs or a severe disruption in the neuronal networks in BCs containing dysplastic lesions. Further studies are needed to elucidate the nature and the potential role(s) of balloon cells in MCD-induced epileptogenicity.

Adolescent↗

PubMed2004

Upregulation of glutamate receptors in rat cerebral cortex with neuronal migration disorders.

Neuronal migration disorders (NMDs) constitute the main pathologic substrate of medically intractable epilepsy in human. This study is designed to investigate the changes in expression of glutamate receptor subtypes on radiation-induced NMD in rats. The lesion was produced by intrauterine irradiation (240 cGy) on E17 rats, and then 10 weeks old rats were used for the study. The pathologic and immuno-histochemical findings for glutamate receptor subunit proteins on NMD cortex were correlated with development of behavioral seizures and EEG abnormality. Spontaneous seizures uncommonly occurred in NMD rats (5%); however, clinical stages of seizures were significantly increased in NMD rats by an administration of kainic acid. Brains taken from irradiated rats revealed gross and histopathologic features of NMD. Focal cortical dysplasia was identified by histopathology and immunohistochemistry with neurofilament protein (NF-M/H). Significantly strong NR1 and NR2A/B immunoreactivities were demonstrated in cytomegalic and heterotopic neurons of NMD rats. The results of the present study indicate that epileptogenesis of NMD might be caused by upregulation of glutamate receptor expression in dysplastic neurons of the rat cerebral cortex with NMDs.

Animals↗

PubMed1998

Determination of somatostatin receptor subtype 2 in carcinoid tumors by immunohistochemical investigation with somatostatin receptor subtype 2 antibodies.

We have shown previously that expression of mRNA for somatostatin receptor subtype 2 (sst2) detected by in situ hybridization correlates to therapeutic outcome in patients with carcinoid tumors treated with somatostatin analogues. However, in situ hybridization is laborious and not practical in clinical routine work. We have, therefore, developed polyclonal antibodies directed against sst2 that may be used for immunohistochemistry on tissue specimens. The staining is specific and is highly correlated to expression of mRNA for sst2 (P < 0.01) as well as to tracer uptake at somatostatin receptor scintigraphy (P < 0.01). There is also a good correlation to the therapeutic response in carcinoid patients treated with somatostatin analogues (P < 0.05). Of 35 patients with carcinoid tumors included in this investigation, 25 stained positive with the antibodies. Twenty-two of these were investigated by somatostatin receptor scintigraphy and showed tracer uptake in metastases. An additional two patients that did not stain with the antibodies showed pathological uptake of the tracer in metastases, which might indicate binding to somatostatin receptor subtype 5. None of the 10 patients without positive immunostaining responded to somatostatin analogue treatment, whereas patients with a positive stain had a biochemical response or remained stable during treatment. Thus, these antibodies may be used to determine the presence of sst2 in carcinoid tumors and to select patients suitable for somatostatin analogue treatment. The method is easily applicable in clinical practice.

Animals↗

PubMed1975

Staging in the therapy of cancer of the breast.

Clinical and pathologic staging of breast cancer are discussed. A new pathologic staging system is presented: numerical scores are assigned, in cases of infiltrating ductal carcinoma of no specific subtype, for tumor size, histologic grade, amount of stromal infilttration, vascular invasion, axillary lymph nodal metastases, and sinus histiocytosis in axillary lymph nodes. Staging by this system correlates well with survival in cases treated by radical mastectomy. The essential features to be studied in pathologic specimens of breast cancer are also indicated.

Breast↗

PubMed2001

Analysis of human papillomavirus in schneiderian papillomas as compared to chronic sinusitis and normal nasal mucosa.

Schneiderian papillomas (SPs) are tumours arising from the surface epithelium (schneiderian epithelium) of the nasal cavity and paranasal sinuses. Evidence points toward a viral etiology, specifically human papillomavirus (HPV). Although substantial data indicate HPV as a likely etiology, little is known about the role of HPV in benign nasal pathologies or in normal nasal mucosa. The objective of this study was to characterize the relationship between HPV and SP, chronic sinusitis (CS), and normal nasal mucosa. A case-control study was undertaken, matching patients with SP to patients with CS. Patients with normal nasal mucosa served as a control group. All patients had their tissues analyzed for the presence of various HPV subtypes using line blot assay. A total of 168 patients were identified (74 SP, 74 CS, 20 control). Of these, 70 (41.7%) had detectable deoxyribonucleic acid and 9 of 70 (12.9%) had detectable HPV of subtypes 6, 11, and 16. None had detectable HPV type 18. Significant differences were detected in the presence of HPV in the CS, SP, and control groups, as well as in the presence of low- versus high-risk subtypes among investigation and control groups. Significant differences exist in HPV infectivity among SP, benign nasal pathologies such as CS, and normal nasal mucosa. Human papillomavirus plays an important role, at least in part, in the development of SP, with types 6, 11, and 16 being more pivotal than other types. Line blot assay is a useful technique in identifying HPV in SP.

Case-Control Studies↗

PubMed2002

Clinical pattern and pathologic stage but not histologic features predict outcome for bronchioloalveolar carcinoma.

BACKGROUND: The histologic criteria defining bronchioloalveolar carcinoma (BAC) were recently revised, but it is unclear whether these criteria predict clinical behavior. This study determined the outcome of resected BAC in relationship to clinical and radiologic disease pattern, and pathologic features. METHODS: Between 1989 and 2000, 100 consecutive surgically treated patients with adenocarcinomas exhibiting various degrees of BAC features were retrospectively studied. Histology was reviewed; tumors were classified as pure BAC, BAC with focal invasion, and adenocarcinoma with BAC features. Clinical and radiologic pattern were classified as unifocal, multifocal, or pneumonic. Demographic data, tumor stage, and outcome were recorded. Survival was analyzed by the Kaplan-Meier method, and prognostic factors were determined by the log-rank test. RESULTS: Patient median age was 65, and 74% of the patients were female. Pure BAC, BAC with focal invasion, and adenocarcinoma with BAC features occurred in 47, 21, and 32 patients, respectively. Unifocal disease occurred in 64 patients, multifocal in 29, and pneumonic in 7. Seventy-one patients had stage I/II tumors, 22 had stage III/IV, and 7 patients had Stage X tumors. Overall 5-year survival was 74%. There was no significant difference in survival among the three histologic subtypes. The pneumonic pattern had significantly worse survival compared with unifocal and multifocal patterns. Pathologic stage predicted survival, with 5-year survivals for I/II and III/IV of 83.7% and 59.6%, respectively. CONCLUSIONS: Clinical pattern and pathologic stage, but not the degree of invasion on histologic examination predict survival. Multifocal disease is associated with excellent long-term survival after resection. The favorable survival of stage III/IV BAC indicates that the current staging system does not fully describe this disease in patients undergoing resection because of its distinct tumor behavior.

Adenocarcinoma, Bronchiolo-Alveolar↗

PubMed2003

Cellular pathology in the dorsolateral prefrontal cortex distinguishes schizophrenia from bipolar disorder.

The classification of schizophrenia and bipolar disorder as two separate disease entities has been hotly debated almost from the moment of its inception with Kraepelin's descriptions of "dementia praecox" and "manic-depressive insanity" in 1896. Kraepelin's nosologic distinction was based on clinical observation of symptomatology and outcome, and even today, despite major advances in science and technology, differential diagnosis of psychosis relies on the clinical course of illness. However, new evidence from diverse fields, e.g., genetics, neuropsychology, and brain imaging, have refueled the debate about whether or not schizophrenia and bipolar disorder represent distinct diseases, leading some to postulate that schizophrenia and bipolar disorder represent different manifestations of psychosis along a continuum with schizoaffective disorder representing an intermediate subtype. To this discourse, we add our own recent postmortem anatomic findings indicating that cellular pathology in the dorsolateral prefrontal cortex in schizophrenia and bipolar disorder differs not just in magnitude but also in direction, in laminar scope, and in relative involvement of neuronal and glial cell types. Thus, distinct morphometric alterations in the dorsolateral prefrontal cortex underlie what appear on neuroimaging analysis to be similar abnormalities in structural and metabolic function in the prefrontal cortex, and the diverse cellular pathology in the dorsolateral prefrontal cortex in these two disorders may account for the greater deficit in schizophrenia on cognitive tasks involving memory, problem solving and abstraction.

Bipolar Disorder↗

PubMed1977

Differentiation of alcoholics. Childhood history of minimal brain dysfunction, family history, and drinking pattern.

Alcoholics were differentiated into two subgroups on the basis of drinking patterns and subjective response to alcohol. Severe drinkers (primary alcoholics) retrospectively reported more symptoms of childhood minimal brain dysfunction than less severe drinkers (secondary alcoholics), psychiatric patients, and normals. The alcoholics as a group reported a greater incidence of familial alcohol abuse than the psychiatric subjects, but a difference on this factor was not observed between the primary and secondary subgroups. In terms of clinical status, the primary alcoholics presented Minnesota Multiphasic Personality Inventory profile more indicative of normality than the other groups, but scored significantly higher on the MacAndrew Alcoholism Scale. These findings are discussed in light of further delineating a specific subtype of alcoholism that may have a genetic-constitutional relationship with other pathological disorders.

Achievement↗

PubMed2000

A(3) adenosine receptor ligands: history and perspectives.

Adenosine regulates many physiological functions through specific cell membrane receptors. On the basis of pharmacological studies and molecular cloning, four different adenosine receptors have been identified and classified as A(1), A(2A), A(2B), and A(3). These adenosine receptors are members of the G-protein-coupled receptor family. While adenosine A(1) and A(2A) receptor subtypes have been pharmacologically characterized through the use of selective ligands, the A(3) adenosine receptor subtype is presently under study in order to better understand its physio-pathological functions. Activation of adenosine A(3) receptors has been shown to stimulate phospholipase C and D and to inhibit adenylate cyclase. Activation of A(3) adenosine receptors also causes the release of inflammatory mediators such as histamine from mast cells. These mediators are responsible for processes such as inflammation and hypotension. It has also been suggested that the A(3) receptor plays an important role in brain ischemia, immunosuppression, and bronchospasm in several animal models. Based on these results, highly selective A(3) adenosine receptor agonists and/or antagonists have been indicated as potential drugs for the treatment of asthma and inflammation, while highly selective agonists have been shown to possess cardioprotective effects. The updated material related to this field of research has been rationalized and arranged in order to offer an overview of the topic.

Animals↗

PubMed1976

Pediatric hodgkin's disease. II. Results of therapy.

Between 1962 and 1972, 79 previously untreated children, aged 15 years and under, with biopsy-proven Hodgkin's disease were seen, evaluated, and treated at Standford University Medical Center. The 5-year actuarial survival for all patients was 89%; relapse-free survival was 66%. No relapse was seen following aggressive treatment with irradiation and MOPP chemotherapy. In patients who were pathologically staged, no relapse was seen beyond 2 years. Patients with mixed cellularity subtype fared surprisingly well as compared to those with the nodular sclerosing subtype. An analysis of the types of treatment administered and complications of therapy suggests that the major difference between children and adults with Hodgkin's disease is the potential for long-term sequelae resulting from aggressive treatment. In an attempt to maximize the quality of survival, a proposal is made for low-dose radiation and planned MOPP chemotherapy.

Adolescent↗

PubMed1997

Non-Hodgkin's lymphoma of the heart in patients infected with human immunodeficiency virus.

A case of HIV-associated cardiac non-Hodgkin's lymphoma (NHL) is described, and the epidemiologic and clinicopathologic features of 21 cases previously reported in the literature are analyzed. All patients were homosexual males, and the cardiac NHL was the first acquired immune deficiency syndrome-defining condition in the majority. Patients were referred with nonspecific clinical findings including dyspnea and tachycardia, but rapid progression of cardiac dysfunction was frequent after symptoms appeared. Echocardiography constitutes the most useful noninvasive procedure in the diagnosis of cardiac NHL. Most of the patients had disseminated diseased at initial presentation; pathologically, the lymphomas were of B lymphocyte origin and of high-grade subtypes. Prognosis of HIV-associated cardiac NHL is generally poor, although clinical remission has been observed with combination chemotherapy. Cardiac lymphomas in HIV-associated patients are typically high-grade and often disseminate early. Although the prognosis is poor, patients in whom dissemination has not occurred could have longer survival under systemic chemotherapy.

Adult↗

PubMed2003

Histopathology of breast cancer among African-American women.

Although the overall incidence of breast cancer in African-American women is lower than in white women, African-American women younger than 50 years old have a higher incidence of breast cancer than white women. African-American women with breast cancer have a poorer survival rate than white women and are more likely to die of breast cancer in almost every age group. To explain this disparity, we studied a substantial body of literature that reported a biologic difference in the tumors found in African-American and white women. Specifically, more aggressive histopathologic patterns have been described among African-American patients with breast cancer when compared with white women. In addition, there are data that support an ethnicity-related variation in the expression of breast tumor hormonal markers. The objective of this study was to critically evaluate the existing published data on the histologic features of breast cancer to determine whether breast cancer in African-American women is a histologically more aggressive disease than in white women. We conclude that the aggressive tumor histology reported in African-American women has not been analyzed carefully with respect to the age of the patient at the time of diagnosis and the stage of disease at presentation. Furthermore, there is a need for central pathology review using accepted, published criteria for diagnosis of uncommon and controversial histologic subtypes of breast cancer.

Adult↗

PubMed1993

Distribution of metallothionein in the human central nervous system.

The distribution of metallothionein (MT), a metal-binding protein, was examined immunohistochemically in the normal human brain and spinal cord. Paraffin-embedded brain tissue from three patients who had died from a non-neurological disease and were free of histopathological central nervous system alterations were processed. The results of the present study demonstrate that MT is readily detectable in a subgroup of astrocytes in the normal human brain. MT staining is most intense on grey matter astrocytes that bear short stout processes and which probably represent protoplasmic astrocytes. Using anti-MT and anti-glial fibrillary acidic protein immunostaining, we could demonstrate two subpopulations of astrocytes that were mutually exclusive. The functional significance of MT-expression in protoplasmic astrocytes is not entirely clear. Metal detoxification is only one of the many postulated functions of MT. The finding that staining for MT permits subtyping of astrocytes may be of great importance in glia research and surgical pathology of the human brain.

Adult↗

PubMed2002

Neuroprotective activity of metabotropic glutamate receptor ligands.

Metabotropic glutamate receptors form a family of currently eight subtypes (mGluR1-8), subdivided into three groups (I-III). Activation of group-II (mGluR2 and -3) or group-III metabotropic glutamate receptors (mGluR4, -6, -7 and -8) has been established to be neuroprotective in vitro and in vivo. In contrast, group-I mGluRs (mGluR1 and -5) need to be antagonized in order to evoke protection. Initially, all neuroprotective mGluR ligands were analogues of L-glutamate. Those compounds were valuable to demonstrate protection in vitro, but showed limited applicability in animal models, particularly in chronic tests, due to low blood-brain-barrier penetration. Recently, systemically active and more potent and selective ligands became available, e.g., the group-II mGluR agonists LY354740 and LY379268 or group-I antagonists like MPEP (mGluR5-selective) and BAY36-7620 (mGluR1-selective). This new generation of pharmacological agents allows a more stringent assessment of the role of individual mGluR-subtypes or groups of receptors in various nervous system disorders, including ischaemia-induced brain damage, traumatic brain injury, Huntington's and Parkinson's-like pathology or epilepsy. Moreover, the use of genetically modified animals (e.g., knock-out mice) is starting to shed light on specific functions of mGluR-subtypes in experimental neuropathologies.

Animals↗

PubMed2006

Fragmentation of Golgi apparatus of nigral neurons with alpha-synuclein-positive inclusions in patients with Parkinson's disease.

We examined whether the Golgi apparatus (GA) is fragmented in nigral neurons in 18 cases with Parkinson's disease (PD) and in 8 control cases. The nigral neurons in cases with PD showed various degrees of Lewy pathology with alpha-synuclein immunohistochemistry, and we divided the neurons into three subtypes according to differences in alpha-synuclein immunoreactivity: (1) neurons without pale bodies or Lewy bodies, (2) neurons with pale bodies, and (3) neurons with Lewy bodies. In controls, we did not observe fragmented GA in nigral neurons by immunocytochemistry with an anti-TGN46 antibody. In PD, the GA was fragmented in 3% of the nigral neurons without inclusions, and in 5% of the neurons with Lewy bodies. In contrast, fragmented GA was noted in 19% of the neurons containing pale bodies. Since pale bodies represent early stages in the development of brainstem Lewy bodies, our results suggest that the cytotoxicity of alpha-synuclein-positive aggregates is reduced in the process of Lewy body formation.

Aged↗